王珍妮, 王珊, 杨超, 李长春, 赵珍珍, 孔祥如, 邓晓斌, 彭亮. 神经母细胞瘤中Hsp27的表达及其与化疗药物关系的研究[J]. 中国肿瘤临床, 2019, 46(23): 1199-1205. DOI: 10.3969/j.issn.1000-8179.2019.23.274
引用本文: 王珍妮, 王珊, 杨超, 李长春, 赵珍珍, 孔祥如, 邓晓斌, 彭亮. 神经母细胞瘤中Hsp27的表达及其与化疗药物关系的研究[J]. 中国肿瘤临床, 2019, 46(23): 1199-1205. DOI: 10.3969/j.issn.1000-8179.2019.23.274
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Wang Zhenni, Wang Shan, Yang Chao, Li Changchun, Zhao Zhenzhen, Kong Xiangru, Deng Xiaobin, Peng Liang. Heat shock protein 27 expression in neuroblastoma and its relationship with chemotherapeutic agents[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2019, 46(23): 1199-1205. DOI: 10.3969/j.issn.1000-8179.2019.23.274
Citation: Wang Zhenni, Wang Shan, Yang Chao, Li Changchun, Zhao Zhenzhen, Kong Xiangru, Deng Xiaobin, Peng Liang. Heat shock protein 27 expression in neuroblastoma and its relationship with chemotherapeutic agents[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2019, 46(23): 1199-1205. DOI: 10.3969/j.issn.1000-8179.2019.23.274
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神经母细胞瘤中Hsp27的表达及其与化疗药物关系的研究

Heat shock protein 27 expression in neuroblastoma and its relationship with chemotherapeutic agents

    摘要
  • 摘要:
      目的  探讨分析热休克蛋白27（heat shock protein 27，Hsp27）与儿童神经母细胞瘤临床病理参数及化疗药物的关系。
      方法  应用免疫组织化学（immunohistochemistry，IHC）法检测90例神经母细胞瘤（neuroblastoma，NB）、24例节细胞神经母细胞瘤（gan-glioneuroblastoma，GNB）和20例节细胞神经瘤（ganglioneuroma，GN）组织中Hsp27蛋白的表达；实时荧光定量PCR（fluorescencequantitative PCR，RT-qPCR）检测59例NB/GNB、5例GN组织标本，及人神经母细胞瘤SH-SY5Y细胞和耐顺铂SH-SY5Y细胞中Hsp27 mRNA的表达；应用IHC或PCR扩增测序法检测其中18例NB/GNB肿瘤标本化疗药物相关性分子靶标。
      结果  Hsp27蛋白在NB/GNB中阳性表达率为64.9%，明显高于GN的0（χ2=28.994，P < 0.05）；在NB/GNB中，Hsp27阳性表达与肿瘤的分期、危险度、转移和预后有关（P < 0.05），与患儿年龄、性别、Shimada组织学分型、N-myc有无扩增无关（P>0.05）；Hsp27 mRNA在NB/GNB中的相对表达量为3.763±1.854，高于GN的2.476±0.698（P>0.05）；Hsp27 mRNA在耐顺铂细胞中的表达明显高于亲代细胞（F=16.246，P < 0.01）。检测化疗药物相关性分子靶标7个，结果显示Hsp27的表达与铂类药物敏感性相关。
      结论  本研究初步显示Hsp27的表达与NB的分期、危险度、转移、预后相关，可能参与了NB/GNB的发生发展转移。Hsp27的表达与铂类敏感性相关，需进一步增大样本量来验证其相关性。

     

    Abstract:
      Objective  To investigate the expression of heat shock protein 27 (Hsp27) in children with neuroblastomas and analyze the relationship of Hsp27 expression and clinicopathological parameters with chemotherapeutic agents.
      Methods  Immunohistochemical (IHC) staining was performed to detect the expression of Hsp27 protein in 90 neuroblastomas (NBs), 24 ganglioneuroblastomas (GNBs), and 20 ganglioneuromas (GNs). Quantitative real-time polymerase chain reaction PCR (RT-qPCR) examinations were performed to detect the expression of mRNA in 59 NBs/GNBs, 5GNs, neuroblastoma cell lines, and drug-resistant cell lines. Immunohistochemical staining, PCR amplification, and sequencing were used to examine the expression or mutation of drug-related genomic markers in 18 NBs/GNBs.
      Results  The positive expression rates of Hsp27 in NBs/GNBs were significantly higher than that in GNs (64.9% vs. 0, χ2=28.994, P < 0.05). In NBs/GNBs, positive Hsp27 expression was associated with tumor stage, risk stratification, metastasis, and prognosis (P < 0.05), but was not associated with age, sex, Shimada classification, or N-MYC (P>0.05). The mRNA levels of Hsp27 in NBs/GNBs were higher than those in GNs (3.763±1.854 vs. 2.476±0.698, P>0.05). The mRNA levels of Hsp27 in the drug-resistant cell line were significantly higher than those in the neuroblastoma cell line (F=16.246, P < 0.01). Seven genomic markers of anti-neoplastic agents were examined, and Hsp27 expression was found to be related to platinum resistance.
      Conclusions  Hsp27 expression was associated with tumor stage, risk stratification, metastasis, and prognosis. Therefore, Hsp27 may promote tumorigenesis, progression, and metastasis. Furthermore, Hsp27 expression is related to platinum resistance. Further studies with larger sample sizes areneeded to verify these correlations.

     

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